Yield 2u globulin is a rat liver protein whose synthesis is under complex hormonal control in vivo. The protein is encoded by a multigene family, comprising 18-20 genes per haploid complement. The cloned genes retain hormonal inducibility when introduced into tissue culture cells with the appropriate hormone receptor. The 5 feet promoter region of yield 2u globulin, when linked to the structural gene for herpes thymidine kinase, confers hormone responsiveness to tk. Site specific mutagenesis of the promotor region will be used to identify those DNA sequences required for hormonal response, and to determine if hormonal response is the result of a positive induction of transcription, or a derepression. It will further be determined if hormonal induction is the result of a disruption of the chromatin structure over an entire region, rather than an induction of transcription from one specific site. The yield 2u-tk hybrid genes will be introduced into tissue culture cells in such a manner as the render tk activity dependent upon hormones. These cell lines will then be used to study the genetics of the hormone response pathways of glucocorticoids and estrogen.